Previous studies demonstrated the existence of both a-MSH and deacetylated alpha-MSH in the same neurons in rat and human brain. The present studies demonstrate that alpha-MSH was 2-3 orders of magnitude more behaviorally potent than the deacetylated peptide in a behavioral paradigm. An enzyme which acetylates alpha-MSH was identified and the regional distribution was investigated. Highest enzyme activities were found in the pituitary gland and brain. Pituitary enzyme activities could be induced by physiological conditions which induce alpha-MSH synthesis. The role of th enzymatic acetylation appears to be in potentiating the alpha-MSH action by decreasing susceptability to peptidase degradation since alpha-MSH has a 5-10 fold longer half-life than deacetylated alpha-MSH in vitro. Another MSH related peptide gamma-MSH has recently been identified in alpha-MSH containing neurons in brain. The behavioral activity of the peptide was examined in a series of studies. Interestingly, gamma-MSH had an opposite behavioral action from alpha-MSH in that alpha-MSH facilitated learning of visual discrimination tasks while gamma-MSH markedly debilitated performance on the maze. The results of these studies demonstrate that one neuron can secrete multi-neurotransmitters with drastically different behavioral actions. The secretory product of the multi-neurotransmitter neuron may be regulated by post-translational processing such as enzymatic acetylation.